dx&tx of DM

1. DIABETES MELLITUS
YAHAYA JJ., DDS

2. Introduction
◦Diabetes mellitus (DM) is a chronic, metabolic disease characterized
by elevated levels of blood sugar, which leads over time to serious
damage to the heart, blood vessels, eyes, kidneys and nerves.
◦The most common is type 2 diabetes mellitus (T2DM), usually it
occurs in adults, and develops when the body becomes resistant to
insulin or doesn't make enough insulin.
◦In the past 3 decades the prevalence of type 2 diabetes has risen
dramatically in countries of all income levels.
◦Type 1 diabetes mellitus (T1DM), once known as juvenile diabetes
or insulin-dependent diabetes, is a chronic condition in which the
pancreas produces little or no insulin by itself.

3. Citation: Glob Health Action 2016, 9: 31440 -
http://dx.doi.org/10.3402/gha.v9.31440

5. JAPAN

6. JAPAN

11. Pathogenesis of DM
 Absolute insulin deficiency (Type 1 DM) occurs with autoimmune destruction of insulin
secreting β-cells (Type 1A DM) and other congenital (genetic defects in the formation or
function of the endocrine pancreas), or acquired (relapsing pancreatitis and pancreatectomy)
conditions.
 Absolute deficiency of insulin action also can occur in the total absence of insulin receptors, a
rare event.

13. T2DM related metabolic
Progressive insulin deficiency thus induces a starvation like state
which is associated with the following metabolic processes:
Excessive hepatic and renal gluconeogenesis
Decreased peripheral utilization of glucose
Hyperglycemia with resultant glycosuria
Loss of water and sodium salts
Proteolysis in muscle liberating amino acids such as alanine and
glutamine as substrates for gluconeogenesis
Uncontrolled lipolysis leads to the rapid mobilization of fatty acids
from adipose tissue and the increased delivery of fatty acids to the
liver leading to the increased synthesis of triglycerides and secretion
of very low-density lipoprotein (VLDL).

14. Pathogenesis of DM
◦Relative insulin deficiency occurs with genetic or acquired
defects in insulin synthesis or secretion that are
inadequate to overcome the resistance caused by fewer
functioning insulin receptors, or resistance to insulin
action induced by stress, drugs, and most commonly
obesity (Type 2 DM)

17. Acute clinical Manifestation/Acute Complications
◦Most of them are a result of hyperglycemia which
exceeds renal threshold to result in polyuria, increased
thirst, dehydration, electrolyte disturbances, weight loss,
and metabolic decompensation, in extreme degree
known as diabetic ketoacidosis and non-ketotic
hyperosmolar coma

18. Chronic Complications
◦The chronic complications include macrovascular
(CAD, CVD, amputations) and microvascular
(retinopathy, nephropathy, neuropathy) lesions

19. Diagnosis of Diabetes
FPG ≥7.0 mmol/L
Fasting = no caloric intake for at least 8 hours
or
A1C ≥6.5% (in adults)
Using a standardized, validated assay in the absence of factors that
affect the accuracy of the A1C and not for suspected type 1 diabetes
or
2hPG in a 75 g OGTT ≥11.1 mmol/L
or
Random PG ≥11.1 mmol/L
Random = any time of the day, without regard to the interval since the
last meal
A1C, glycated hemoglobin; FPG, fasting plasma glucose; PG, plasma glucose

21. Confirmatory test required
• In the absence of symptomatic hyperglycemia, if a
single lab test result is in the diabetes range, a repeat
confirmatory lab test (FPG, A1C, 2hPG in a 75 g OGTT)
must be done on another day
• Repeat the same test (in a timely fashion) to confirm
• But a random PG in the diabetes range in an
asymptomatic individual should be confirmed with an
alternate test
• If results of two different tests are available and both
are above the diagnostic thresholds, the diagnosis of
diabetes is confirmed
2hPG, 2-hour plasma glucose; AlC, glycated hemoglobin; FPG, fasting plasma glucose;
OGTT, oral glucose tolerance test; PG, plasma glucose.

22. Confirmatory test NOT required
• In the case of symptomatic hyperglycemia, the
diagnosis has been made and a confirmatory test is
not required before treatment is initiated.
• To avoid rapid metabolic deterioration in individuals in
whom type 1 diabetes is likely (younger or lean or
symptomatic hyperglycemia, especially with ketonuria
or ketonemia), the initiation of treatment should not be
delayed in order to complete confirmatory testing
2hPG, 2-hour plasma glucose; AlC, glycated hemoglobin; FPG, fasting plasma glucose;
OGTT, oral glucose tolerance test; PG, plasma glucose.

23. Pros and Cons of Diagnostic Tests
Test Advantages Disadvantages
FPG Established standard
Fast and easy
Single Sample
Sample not stable
Day-to-day variability
Inconvenient to fast
Glucose homeostasis in single time point
2hPG in
75 g
OGTT
Established standard Sample not stable
Day-to-day variability
Inconvenient, Unpalatable
Cost
A1C Convenient
Single sample
Low day-to-day variability
Reflects long term glucose
$$$
Affected by medical conditions, aging,
ethnicity
Standardized, validated assay required
Not applicable to every patient type
A1C, glycated hemoglobin; FPG, fasting plasma glucose; PG, plasma glucose

24. Dealing with discordance in results
Many people identified as
having diabetes using A1C
will not be identified as
having diabetes by
traditional glucose criteria,
and vice versa.
When results of more than one test are available (FPG, A1C, 2hPG
in a 75-g OGTT) and the results are discordant, the test whose
result is above diagnostic cut-point should be repeated, and the
diagnosis made on basis of the repeat test.
FPG 2hPG
A1C
A1C, glycated hemoglobin; FPG, fasting plasma glucose; OGTT, oral glucose tolerance
test; PG, plasma glucose

25. Diagnosis of prediabetes
Tests Result Prediabetes
category
Fasting plasma
glucose (mmol/L)
6.1-6.9 IFG
2h PG in a 75g
OGTT (mmol/L)
7.8-11.0 IGT
A1C (%) 6.0-6.4 Prediabetes
2hPG, 2-hour plasma glucose; AlC, glycated hemoglobin; FPG, fasting plasma glucose; IFG, impaired fasting
glucose; IGT, impaired glucose tolerance; OGTT, oral glucose tolerance test.

26. A1C Level and Future Risk of Diabetes:
Systematic Review
A1C Category (%)
5-year incidence of
diabetes
5.0-5.5 <5 to 9%
5.5-6.0 9 to 25%
6.0-6.5 25 to 50%
Zhang X et al. Diabetes Care. 2010;33:1665-1673.
A1C, glycated hemoglobin

27. Definition of Metabolic Syndrome
Measure Categorical thresholds
Elevated waist circumference (population/country specific)
Canada, United States of America
Middle Eastern, Sub-Saharan African, Mediterranean,
Europids
Asians, Japanese, South and Central Americans
Men Women
≥102 cm
≥94 cm
≥90 cm
≥88 cm
≥80 cm
≥80 cm
Elevated TG (drug treatment for elevated TG is an alternate
indicator†)
≥1.7 mmol/L
Reduced HDL-C (drug treatment for reduced HDL-C is an
alternate indicator†)
<1.0 mmol/L in males;
<1.3 mmol/L in females
Elevated BP (antihypertensive drug treatment in a person with
a history of hypertension is an alternate indicator)
systolic ≥130 mmHg or
diastolic ≥85 mmHg
Elevated FPG (drug treatment of elevated glucose is an
alternate indicator)
≥5.6 mmol/L
Adapted from: Alberti KG, et al. Circulation 2009;120:1640
† Commonly used drugs for elevated TG and reduced HDL-C are fibrates and nicotinic acid. A person taking one of these
drugs can be presumed to have high TG and reduced HDL-C. High-dose omega-3 fatty acids presumes high TG

28. Definition of Metabolic Syndrome
Measure Categorical thresholds
Elevated waist circumference (population/country specific)
Canada, United States of America
Middle Eastern, Sub-Saharan African, Mediterranean,
Europids
Asians, Japanese, South and Central Americans
Men Women
≥102 cm
≥94 cm
≥90 cm
≥88 cm
≥80 cm
≥80 cm
Elevated TG (drug treatment for elevated TG is an alternate
indicator†)
≥1.7 mmol/L
Reduced HDL-C (drug treatment for reduced HDL-C is an
alternate indicator†)
<1.0 mmol/L in males;
<1.3 mmol/L in females
Elevated BP (antihypertensive drug treatment in a person with
a history of hypertension is an alternate indicator)
systolic ≥130 mmHg or
diastolic ≥85 mmHg
Elevated FPG (drug treatment of elevated glucose is an
alternate indicator)
≥5.6 mmol/L
Adapted from: Alberti KG, et al. Circulation 2009;120:1640
† Commonly used drugs for elevated TG and reduced HDL-C are fibrates and nicotinic acid. A person taking one of these
drugs can be presumed to have high TG and reduced HDL-C. High-dose omega-3 fatty acids presumes high TG

29. Recommendation 1
1.Diabetes should be diagnosed by any of the following
criteria:
◦ FPG ≥7.0 mmol/L [Grade B, Level 2]
◦ A1C ≥6.5% (for use in adults in the absence of factors that
affect the accuracy of A1C and not for use in those with
suspected type 1 diabetes) [Grade B, Level 2]
◦ 2hPG in a 75 g OGTT ≥11.1 mmol/L [Grade B, Level 2]
◦ Random PG ≥11.1 mmol/L [Grade D, Consensus]

30. Recommendation 1 cont’d
◦ In the presence of symptoms of hyperglycemia, a
single test result in the diabetes range is sufficient to
make the diagnosis of diabetes.
◦ In the absence of symptoms of hyperglycemia, if a
single laboratory test result is in the diabetes range, a
repeat confirmatory laboratory test (FPG, A1C, 2hPG
in a 75 g OGTT) must be done on another day

31. Recommendation 1 cont’d
◦ It is preferable that the same test be repeated (in a
timely fashion) for confirmation, but a random PG in
the diabetes range in an asymptomatic individual
should be confirmed with an alternate test.
◦ If results of two different tests are available and both
are above the diagnostic cut-points, the diagnosis of
diabetes is confirmed [Grade D, Consensus]

32. ◦ To avoid rapid metabolic deterioration in individuals in
whom type 1 diabetes is likely (younger or lean or
symptomatic hyperglycemia, especially with ketonuria or
ketonemia), the initiation of treatment should not be
delayed in order to complete confirmatory testing [Grade
D, Consensus]
Recommendation 1 cont’d

33. Recommendation 2
2. Prediabetes (defined as a state which places
individuals at high risk of developing diabetes and its
complications) is diagnosed by any of the following
criteria:
◦ IFG (FPG 6.1-6.9 mmol/L) [Grade A, Level 1]
◦ IGT (2hPG in a 75 g OGTT 7.8-11.0 mmol/L) [Grade A, Level
1]
◦ A1C 6.0%-6.4% (for use in adults in the absence of factors
that affect the accuracy of A1C and not for use in suspected
type 1 diabetes) [Grade B, Level 2]

34. Key Messages
◦ The chronic hyperglycemia of diabetes is associated with
significant long-term microvascular and CV complications
◦ A FPG of ≥7.0 mmol/L, a 2hPG value in a 75 g OGTT of
≥11.1 mmol/L or an A1C of ≥6.5% can predict the
development of retinopathy. This permits the diagnosis of
diabetes to be made on the basis of each of these
parameters
2018 Diabetes Canada CPG – Chapter 3. Definition, Diagnosis & Classification of Diabetes, Prediabetes, Metabolic Syndrome

35. Key Messages
◦ The term "prediabetes" refers to impaired fasting glucose,
impaired glucose tolerance or an A1C of 6.0% to 6.4%,
each of which places individuals at increased risk of
developing diabetes and its complications
2018 Diabetes Canada CPG – Chapter 3. Definition, Diagnosis & Classification of Diabetes, Prediabetes, Metabolic Syndrome

36. Key Messages for People with
Diabetes
◦ There are two main types of diabetes. Type 1 diabetes
occurs when the pancreas is unable to produce insulin.
Type 2 diabetes occurs when the pancreas does not
produce enough insulin or when the body does not
effectively use the insulin that is produced
◦ Gestational diabetes is a type of diabetes that is first
recognized or begins during pregnancy
◦ Monogenic diabetes is a rare disorder caused by genetic
defects of beta cell function
2018 Diabetes Canada CPG – Chapter 3. Definition, Diagnosis & Classification of Diabetes, Prediabetes, Metabolic Syndrome

37. Key Messages for People with Diabetes
◦ Prediabetes refers to blood glucose levels that are higher
than normal, but not yet high enough to be diagnosed as
type 2 diabetes. Although not everyone with prediabetes
will develop type 2 diabetes, many people will
◦ You should discuss the type of diabetes you have with
your diabetes health-care team
◦ There are several types of blood tests that can be done to
determine if a person has diabetes and, in most cases, a
confirmatory blood test is required to be sure